Interaction of hydrogen sulfide with ion channels

Tang, Guanghua; Wu, Lingyun; Wang, Rui

doi:10.1111/j.1440-1681.2010.05351.x

Cited by 145 publications

(163 citation statements)

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“…In addition to TRPA1 receptors, H 2 S has been identified as an endogenous ligand of several receptors/channels that might also participate in nociceptor sensitization and hyperalgesia under various experimental conditions (8,11,33,38). For example, the suppression of sustained potassium channel currents has been suggested to be responsible for the NaHS-induced sensitization of rat trigeminal ganglion neurons innervating the temporomandibular joints (11).…”

Section: Discussionmentioning

confidence: 99%

Hydrogen sulfide induces hypersensitivity of rat capsaicin-sensitive lung vagal neurons: role of TRPA1 receptors

Hsu

Lin

Lee

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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-The sensitization of capsaicin-sensitive lung vagal (CSLV) afferents by inflammatory mediators is important in the development of airway hypersensitivity. Hydrogen sulfide (H 2 S) is an endogenous mediator inducing hyperalgesia through transient receptor potential ankyrin 1 (TRPA1) receptors located on nociceptors. We conducted this study to determine whether H 2S elevates the sensitivity of rat CSLV afferents. In anesthetized, artificially ventilated rats, the inhalation of aerosolized sodium hydrosulfide (NaHS, a H2S donor) caused no significant changes in the baseline activity of CSLV afferents. However, the afferent responses to right atrial injection of capsaicin or phenylbiguanide and to lung inflation were all markedly potentiated after NaHS inhalation. By contrast, the inhalation of its vehicle or NaOH (with a similar pH to NaHS) failed to enhance the afferent responses. Additionally, the potentiating effect on the afferent responses was found in rats inhaling L-cysteine (a substrate of H2S synthase) that slowly releases H2S. The potentiating effect of NaHS on the sensitivity of CSLV afferents was completely blocked by pretreatment of HC-030031 (a TRPA1 receptor antagonist) but was unaffected by its vehicle. In isolated rat CSLV neurons, the perfusion of NaHS alone did not influence the intracellular Ca 2ϩ concentration but markedly potentiated the Ca 2ϩ transients evoked by capsaicin. The NaHScaused effect was totally abolished by HC-030031 pretreatment. These results suggest that H2S induces a nonspecific sensitizing effect on CSLV fibers to both chemical and mechanical stimulation in rat lungs, which appears mediated through an action on the TRPA1 receptors expressed on the nerve endings of CSLV afferents. lung; lung vagal C fibers; afferent sensitization; H2S; TRPA1 receptors CAPSAICIN-SENSITIVE LUNG VAGAL (CSLV) afferents are nociceptive-like free nerve endings innervating all levels of the respiratory tract. CSLV afferents can detect several inhaled irritants (22, 25) and inflammatory mediators (16,25,26,39) that might in turn trigger various respiratory reflexes such as cough, mucus secretion, and bronchoconstriction (7,22). The afferents are sensitized by several mediators released because of lung inflammation (2,7,15,27), which might then exaggerate these respiratory reflexes. Therefore, the sensitization of CSLV afferents is probably involved in the pathogenesis of airway hypersensitivity in diseases such as chronic cough and asthma (7, 26, 47).Hydrogen sulfide (H 2 S), an irritant gas with the smell of rotten eggs, is emitted principally from volcanoes, hot springs, and numerous industrial sites. Lung exposure to H 2 S might lead to adverse respiratory effects, such as cough, airway irritation, airway hypersensitivity, and lung inflammation (16, 37, 41). Therefore, for the past decades, H 2 S was generally considered only an exogenous irritant. However, beginning with a report in 1996, H 2 S was suggested to act as an endogenous neuromodulator facilitating the hippocampal long-term potentiati...

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Section: Discussionmentioning

confidence: 99%

Hydrogen sulfide induces hypersensitivity of rat capsaicin-sensitive lung vagal neurons: role of TRPA1 receptors

Hsu

Lin

Lee

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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“…CBS and CSE are differentially expressed in cardiovascular as well as in several other body districts (13). The physiological functions of H 2 S are mediated by a variety of molecular targets, including ion channels and signaling proteins (16)(17)(18). Alterations in H 2 S metabolism contribute to an array of cardiovascular disorders such as hypertension, atherosclerosis, heart failure, and diabetes (19).…”

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confidence: 99%

Hydrogen sulphide pathway contributes to the enhanced human platelet aggregation in hyperhomocysteinemia

Bianca

Mitidieri

Minno

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Homocysteine is metabolized to methionine by the action of 5,10methylenetetrahydrofolate reductase (MTHFR). Alternatively, by thetransulfuration pathway, homocysteine is transformed to hydrogen sulphide (H2S),through multiple steps involving cystathionine beta-synthase and cystathioninegamma-lyase. Here we have evaluated the involvement of H2S in the thromboticevents associated with hyperhomocysteinemia. To this purpose we have usedplatelets harvested from healthy volunteers or patients newly diagnosed withhyperhomocysteinemia with a C677T polymorphism of the MTHFR gene (MTHFR++). NaHS(0.1-100 microM) or l-cysteine (0.1-100 microM) significantly increased plateletaggregation harvested from healthy volunteers induced by thrombin receptoractivator peptide-6 amide (2 microM) in a concentration-dependent manner. Thisincrease was significantly potentiated in platelets harvested from MTHFR++carriers, and it was reversed by the inhibition of either cystathioninebeta-synthase or cystathionine gamma-lyase. Similarly, in MTHFR++ carriers, thecontent of H2S was significantly higher in either platelets or plasma comparedwith healthy volunteers. Interestingly, thromboxane A2 production was markedlyincreased in response to both NaHS or l-cysteine in platelets of healthyvolunteers. The inhibition of phospholipase A2, cyclooxygenase, or blockade ofthe thromboxane receptor markedly reduced the effects of H2S. Finally,phosphorylated-phospholipase A2 expression was significantly higher in MTHFR++carriers compared with healthy volunteers. In conclusion, the H2S pathway isinvolved in the prothrombotic events occurring in hyperhomocysteinemic patients

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“…Hydrogen sulfide (H 2 S) targets different ion channels and receptors, and fulfills its various roles in modulating the functions of different systems (19). It appears to be involved in numerous biological processes, including regulation of blood pressure and vascular tone.…”

Section: █ Discussionmentioning

confidence: 99%